期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1865, 期 5, 页码 675-683出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2018.02.003
关键词
Senescence; Mitotic catastrophe; Histone deacetylase 6; 2,4-Di-tert-butylphenol
资金
- National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [2016R1A2B4016005]
- National Research Foundation of Korea [2016R1A2B4016005] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The natural product 2,4-di-tert-butylphenol (DTBP) has a wide spectrum of biological functions, including anticancer activities, although the underlying mechanisms are poorly understood. Here, we found that DTBP induces senescence in human gastric adenocarcinoma AGS cells as evidenced by upregulation of p21 and Rb and increased beta-galactosidase activity. DTBP also induces mitotic catastrophe and generates multinucleated cells, which is accompanied by an increase in the proportion of polymerized tubulin, possibly caused by inhibition of HDAC6 enzyme activity. In silico docking analysis showed that DTBP docked at the entrance of the ligand-binding pocket of the HDAC6 enzyme. Accordingly, DTBP represents a promising lead structure for the development of HDAC6 inhibitors, with an improvement in specificity conferred by modification of the cap group. We propose for the first time that the underlying mechanism of the anticancer activity of DTBP is attributed to inhibition of HDAC6 activity.
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